The analysis of single molecules or thin layers thereof is of both technological and scientific importance. There are a few methods which can unambiguously identify a-priori unknown little quantities of material down to single molecules. However, all these methods suffer from some shortcomings, and therefore have not been technologically implemented yet. General reasons are low sensitivities of the analytical methods and the instability of thin molecular layers and especially single molecules with respect to their thermal, chemical and photo-degradation or to external mechanical fields caused, e.g., by scanning probe microscopy (SPM) tips. Therefore it would be advantageous to improve these methods.
A few modifications of Surface Enhanced Raman Spectroscopy (SERS) can provide Raman spectra of small molecular quantities down to single molecules. A Raman spectrum is a “fingerprint” of a molecule. However, without surface enhancement the probability for a photon to be Raman scattered is very low, such that only large material quantities can be analyzed. On the one hand SERS is based on electromagnetic field enhancement by nano-structures made of plasmon active materials, and on the other hand on some chemical interaction between the surface and the molecule. A surface roughened in a certain manner has a few “active” sites, which enhance the Raman signal substantially to detect it even from single molecules located at the sites. One of the disadvantages of the above described method is the random nature of the active sites. One cannot analyze any molecule at will, since the active sites are usually not precisely known, and, e.g., the molecules have to interact in a particular way with the active sites. The above-mentioned disadvantage can be overcome by precisely fabricated nano-structures. Modern lithography methods do not allow, however, building highly efficient nano-structures reproducibly, since efficient field enhancement requires nanometer precision, which cannot be provided by, e.g., electron beam lithography.
A further disadvantage of prior art SERS is the strong difference between the Raman spectra in solution and the SERS Raman spectra, which are attributed, to some extent, to a specific chemical interaction between the molecule and the SERS active material. Also the molecules have to be placed precisely into the nano-structures to be analyzed.
The above-mentioned disadvantages may be overcome to some extent by the so called Tip Enhanced Raman Spectroscopy (TERS). TERS employs a sharp tip made of a plasmon active material. The tip is placed over an area of interest and enhances Raman scattering of molecules located in the nearest proximity to the tip apex. TERS has its own difficulties: one has to position the tip with high precision in order not to damage the molecules on the surface.
Similarly to TERS and SERS, also infrared spectra of molecules can be enhanced with plasmon active structures. The enhancement is not as strong as for Raman spectroscopy in the visible range, and a single molecule analysis is yet to be demonstrated.
A common disadvantage of all the above-described methods is the large amount of heat produced by the focused plasmon localized at the active site, i.e. high temperatures can cause oxidative damage to the molecules.